Cephalosporins are an important group of broad spectrum antibiotics which are widely used in treatment of bacterial infections. Compounds which have had commercial success are classified as semisynthetic in that they are obtained by chemical modification of a central nucleus which is obtained from natural sources. As in most chemical modifications, the products are obtained together with other materials referred to as impurities which must be removed. Processes used previously to purify the crude products have been inefficient in the production of pharmaceutically acceptable material. These processes include solvent extractions, use of ion exchange resins, chromatography on conventional adsorbents, salting out procedures, or use of activated charcoal.
I have now found that synthetic macroreticular polymeric adsorbents are useful to rapidly and efficiently remove the impurities and give high recovery yields of semisynthetic cephalosporin products and their intermediate derivatives, all of which have a free carboxylic acid group.
The resins and processes related to their use are disclosed in U.S. Pat. Nos. 3,531,463; 3,663,467; and 3,725,400. The disclosed processes relate to isolation of water-soluble organic compounds from a dilute water solution or to removal of organic impurities from aqueous effluent. The decolorization of raw sugar has been disclosed.
It is an object of this invention to provide a process for improving the purity of semisynthetic cephalosporins and their derivatives with minimal loss of material.
Another object of this invention is to provide a process involving the use of nonionic polymeric adsorbents to purify semisynthetic cephalosporins and their derivatives.
A further object of this invention is to run the purification process at controlled pH for maximum efficiency.
Other objects of the invention will be apparent from the full disclosure.